Synthesis of 2H-Chromenes via Hydrazine-Catalyzed Ring-Closing Carbonyl-Olefin Metathesis

Abstract

The catalytic ring-closing carbonyl-olefin metathesis (RCCOM) of O-allyl salicylaldehydes to form 2H-chromenes is described. The method utilizes a [2.2.1]-bicyclic hydrazine catalyst and operates via a [3 + 2]/retro-[3 + 2] metathesis manifold. The nature of the allyl substitution pattern was found to be crucial, with sterically demanding groups such as adamantylidene or diethylidene offering optimal outcomes. A survey of substrate scope is shown along with a discussion of mechanism supported by DFT calculations. Steric pressure arising from syn-pentane minimization of the diethylidene moiety is proposed to facilitate cycloreversion.

AuCl3‐Catalyzed Ring‐Closing Carbonyl–Olefin Metathesis

“…In pioneering studies in 2012, Lambert established an organocatalytic [3+2]/retro [3+2]‐cycloaddition approach to the synthesis of γ,δ‐unsaturated aldehydes through carbonyl–olefin metathesis reactions, but the requirement of highly strained cyclopropenes as olefin components and the tedious preparation of the starting materials impeded its application (Scheme a) . Lambert has subsequently extended this strategy to the synthesis of 2H‐chromenes …”

Ring-opening carbonyl–olefin metathesis of norbornenes

“…At the present time, however, this area is still in its infancy, and the generality of available catalytic platforms falls far short of what would be needed to realize many of the potential applications of this reaction. Recent exciting developments in the use of organocatalysts, 8,9 Lewis acids, [10][11][12][13][14][15][16][17][18][19][20][21] and Brønsted acids 22,23 notwithstanding, this area requires breakthrough advances in catalyst and strategy design if it is to approach the levels of utility realized by other mature catalytic processes.…”

“…Toward this goal, we had previously reported the rst catalytic strategy for carbonyl-olen metathesis. 8,9 This approach was based on the concept of utilizing reversible, locally symmetric, 1,3-dipolar cycloadditions 24 to circumvent some of the difficulties presented by [2 + 2] cycloadditions of carbonyls and alkenes (Fig. 1b).…”

“…27 With this approach, we were able to realize the catalytic ring-opening carbonyl-olen metathesis (ROCOM) of cyclopropenes. 8 Although we have recently expanded this chemistry to ring-closing carbonyl-olen metathesis (RCCOM) reactions as well, 9 for ring-opening reactions this method was effectively limited to cyclopropenes, the high strain of which 28,29 enabled facile cycloreversion of what are otherwise quite stable cycloadducts. Indeed, computational evaluation of a variety of olens revealed that the activation energy of cycloreversion for less strained olens was typically >33 kcal mol À1 .…”

Superelectrophilic Aluminum(III)-Ion Pairs Promote a Distinct Reaction Path for Carbonyl-Olefin Metathesis of Medium-Sized Rings

“…Catalytic carbonyl-olefin metathesis reactions have seen amplified interest within recent years as a result of their potential for direct carbon-carbon bond formation between carbonyl and olefin precursors. [1][2][3] Among the advancement in design principles for carbonyl-olefin metathesis 4 are Lewis acid-catalyzed approaches [5][6][7][8][9] that rely on [2+2]-cycloadditions between carbonyl and olefin functionalities to form intermediate oxetanes. This strategy allows for the development of carbonyl-olefin ringclosing, ring-opening, and cross metathesis reactions, however restrictions currently exist for these examples that hamper their synthetic generality.…”